The applicant's overall goal is to understand the pathogenesis and discover the etiology of systemic lupus erythematosus. During the last funding period, the applicant and his colleagues explored the structure of the Y RNAs that are components of the Ro ribonucleoprotein lupus autoantigen. Y RNAs from a number of species were sequenced, their evolutionarily conserved secondary structures established, and a number of conserved sequence motifs were described. The goal is now to look for an infectious agent that might be important in the etiology of lupus. The preliminary data with sera from pediatric lupus patients strongly suggest an association with Epstein Barr Virus (EBV) infection. Using the Army/Navy repository of sera from military personnel, the applicant will, prospectively, study stored sera from a cohort of 265 initially healthy individuals who would have later developed lupus. Four matched healthy controls and an Asthma patient control for every lupus case will be studied in a similar manner. The applicant will test whether serologic conversion against EBV is more frequent in individuals who later develop clinical and serological evidence of lupus than in matched controls. In other words, the applicant hopes to study progression from immunity to EBV to lupus humoral autoimmunity and subsequent clinical disease. Preliminary results suggest that the serologic fine specificity of the immune response to EBV in lupus patients might be different from normal subjects; such information may identify preclinical subjects who are at risk for developing lupus. This link with antibody response to EBV could provide insight pathogenic mechanisms associated with systemic lupus erythematosus.